NDC 60429-020 Ketoconazole

Ketoconazole

NDC Product Code 60429-020

NDC CODE: 60429-020

Proprietary Name: Ketoconazole What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Ketoconazole What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This medication is used to control dandruff. Use of this medication may help to relieve the flaking, scaling and itching associated with dandruff. Ketoconazole is an azole antifungal that works by preventing the growth of fungus. Ketoconazole 2% shampoo is also used to treat a skin condition known as pityriasis (tinea versicolor), a fungal infection that causes a lightening or darkening of the skin of the neck, chest, arms, or legs.

Product Characteristics

Color(s):
WHITE (C48325 - WHITE TO OFF-WHITE)
Shape: ROUND (C48348)
Size(s):
11 MM
Imprint(s):
T57
Score: 2

NDC Code Structure

  • 60429 - Golden State Medical Supply Inc.

NDC 60429-020-01

Package Description: 100 TABLET in 1 BOTTLE

NDC Product Information

Ketoconazole with NDC 60429-020 is a a human prescription drug product labeled by Golden State Medical Supply Inc.. The generic name of Ketoconazole is ketoconazole. The product's dosage form is tablet and is administered via oral form.

Labeler Name: Golden State Medical Supply Inc.

Dosage Form: Tablet - A solid dosage form containing medicinal substances with or without suitable diluents.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Ketoconazole Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • KETOCONAZOLE 200 mg/1

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • COLLOIDAL SILICON DIOXIDE (UNII: ETJ7Z6XBU4)
  • STARCH, CORN (UNII: O8232NY3SJ)
  • LACTOSE MONOHYDRATE (UNII: EWQ57Q8I5X)
  • MAGNESIUM STEARATE (UNII: 70097M6I30)
  • CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U)
  • POVIDONE (UNII: FZ989GH94E)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Oral - Administration to or by way of the mouth.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Azole Antifungal - [EPC] (Established Pharmacologic Class)
  • Azoles - [CS]
  • Cytochrome P450 3A4 Inhibitors - [MoA] (Mechanism of Action)
  • Cytochrome P450 3A5 Inhibitors - [MoA] (Mechanism of Action)
  • P-Glycoprotein Inhibitors - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Golden State Medical Supply Inc.
Labeler Code: 60429
FDA Application Number: ANDA075319 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 06-15-1999 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Information for Patients

Ketoconazole

Ketoconazole is pronounced as (kee toe kon' na zole)

Why is ketoconazole medication prescribed?
Ketoconazole is used to treat fungal infections when other medications are not available or cannot be tolerated. Ketoconazole should not be used to treat fungal meningiti...
[Read More]

* Please review the disclaimer below.

Ketoconazole Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

Rx only

Prompt recognition of liver injury is essential. Liver function tests (such as SGGT, alkaline phosphatase, SGPT, SGOT and bilirubin) should be measured before starting treatment and at frequent intervals during treatment. Patients receiving ketoconazole tablets concurrently with other potentially hepatotoxic drugs should be carefully monitored, particularly those patients requiring prolonged therapy or those who have had a history of liver disease.Most of the reported cases of hepatic toxicity have to date been in patients treated for onychomycosis. Of 180 patients worldwide developing idiosyncratic liver dysfunction during ketoconazole tablet therapy, 61.3% had onychomycosis and 16.8% had chronic recalcitrant dermatophytoses.Transient minor elevations in liver enzymes have occurred during treatment with ketoconazole tablets. The drug should be discontinued if these persist, if the abnormalities worsen, or if the abnormalities become accompanied by symptoms of possible liver injury.In rare cases anaphylaxis has been reported after the first dose. Several cases of hypersensitivity reactions including urticaria have also been reported.Coadministration of ketoconazole tablets and terfenadine has led to elevated plasma concentrations of terfenadine which may prolong QT intervals, sometimes resulting in life-threatening cardiac dysrhythmias. Cases of torsades de pointes and other serious ventricular dysrhythmias, in rare cases leading to fatality, have been reported among patients taking terfenadine concurrently with ketoconazole tablets. Coadministration of ketoconazole tablets and terfenadine is contraindicated.Coadministration of astemizole with ketoconazole tablets is contraindicated. (See BOX WARNING, CONTRAINDICATIONS, and PRECAUTIONS sections.)Concomitant administration of ketoconazole tablets with cisapride is contraindicated because it has resulted in markedly elevated cisapride plasma concentrations and prolonged QT interval, and has rarely been associated with ventricular arrhythmias and torsades de pointes. (See BOX WARNING, CONTRAINDICATIONS, and PRECAUTIONS sections.)In European clinical trials involving 350 patients with metastatic prostatic cancer, eleven deaths were reported within two weeks of starting treatment with high doses of ketoconazole tablets (1200 mg/day). It is not possible to ascertain from the information available whether death was related to ketoconazole therapy in these patients with serious underlying disease. However, high doses of ketoconazole tablets are known to suppress adrenal corticosteroid secretion.In female rats treated three to six months with ketoconazole at dose levels of 80 mg/kg and higher, increased fragility of long bones, in some cases leading to fracture, was seen. The maximum "no-effect" dose level in these studies was 20 mg/kg (2.5 times the maximum recommended human dose). The mechanism responsible for this phenomenon is obscure. Limited studies in dogs failed to demonstrate such an effect on the metacarpals and ribs.

Description

Ketoconazole is a synthetic broad-spectrum antifungal agent. Each tablet, for oral administration, contains 200 mg ketoconazole base. In addition, each tablet contains the following inactive ingredients: colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and povidone. Ketoconazole is cis-1-Acetyl-4-[p-[[2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-piperazine and has the following structural formula:Ketoconazole is a white to slightly beige, odorless powder, soluble in acids with a molecular formula of C26H28Cl2N4O4 and a molecular weight of 531.44.

Clinical Pharmacology

Mean peak plasma levels of approximately 3.5 mcg/mL are reached within 1 to 2 hours, following oral administration of a single 200 mg dose taken with a meal. Subsequent plasma elimination is biphasic with a half-life of 2 hours during the first 10 hours and 8 hours thereafter. Following absorption from the gastrointestinal tract, ketoconazole is converted into several inactive metabolites. The major identified metabolic pathways are oxidation and degradation of the imidazole and piperazine rings, oxidative O-dealkylation and aromatic hydroxylation. About 13% of the dose is excreted in the urine, of which 2 to 4% is unchanged drug. The major route of excretion is through the bile into the intestinal tract. In vitro, the plasma protein binding is about 99% mainly to the albumin fraction. Only a negligible proportion of ketoconazole reaches the cerebral-spinal fluid. Ketoconazole is a weak dibasic agent and thus requires acidity for dissolution and absorption.Ketoconazole tablets are active against clinical infections with Blastomyces dermatitidis, Candida spp., Coccidioides immitis, Histoplasma capsulatum, Paracoccidioides brasiliensis, and Phialophora spp. Ketoconazole tablets are also active against Trichophyton spp., Epidermophyton spp., and Microsporum spp. Ketoconazole is also active in vitro against a variety of fungi and yeast. In animal models, activity has been demonstrated against Candida spp., Blastomyces dermatitidis, Histoplasma capsulatum, Malassezia furfur, Coccidioides immitis, and Cryptococcus neoformans.

Mode Of Action

In vitro studies suggest that ketoconazole impairs the synthesis of ergosterol, which is a vital component of fungal cell membranes.

Indications And Usage

Ketoconazole tablets are indicated for the treatment of the following systemic fungal infections: candidiasis, chronic mucocutaneous candidiasis, oral thrush, candiduria, blastomycosis, coccidioidomycosis, histoplasmosis, chromomycosis, and paracoccidioidomycosis. Ketoconazole tablets should not be used for fungal meningitis because it penetrates poorly into the cerebral-spinal fluid.Ketoconazole tablets are also indicated for the treatment of patients with severe recalcitrant cutaneous dermatophyte infections who have not responded to topical therapy or oral griseofulvin, or who are unable to take griseofulvin.

Contraindications

Coadministration of terfenadine or astemizole with ketoconazole tablets is contraindicated. (See BOX WARNING, WARNINGS, and PRECAUTIONS sections.)Concomitant administration of ketoconazole tablets with cisapride is contraindicated. (See BOX WARNING, WARNINGS, and PRECAUTIONS sections.)Concomitant administration of ketoconazole tablets with oral triazolam is contraindicated. (See PRECAUTIONS section.)Ketoconazole is contraindicated in patients who have shown hypersensitivity to the drug.

Boxed Warning Section

Hepatotoxicity, primarily of the hepatocellular type, has been associated with the use of ketoconazole tablets, including rare fatalities. The reported incidence of hepatotoxicity has been about 1:10,000 exposed patients, but this probably represents some degree of under-reporting, as is the case for most reported adverse reactions to drugs. The median duration of ketoconazole tablet therapy in patients who developed symptomatic hepatotoxicity was about 28 days, although the range extended to as low as 3 days. The hepatic injury has usually, but not always, been reversible upon discontinuation of ketoconazole tablet treatment. Several cases of hepatitis have been reported in children.

General

Ketoconazole tablets have been demonstrated to lower serum testosterone. Once therapy with ketoconazole tablets has been discontinued, serum testosterone levels return to baseline values. Testosterone levels are impaired with doses of 800 mg per day and abolished by 1600 mg per day. Ketoconazole tablets also decrease ACTH induced corticosteroid serum levels at similar high doses. The recommended dose of 200 mg - 400 mg daily should be followed closely.In four subjects with drug-induced achlorhydria, a marked reduction in ketoconazole absorption was observed. Ketoconazole tablets require acidity for dissolution. If concomitant antacids, anticholinergics, and H2-blockers are needed, they should be given at least two hours after administration of ketoconazole tablets. In cases of achlorhydria, the patients should be instructed to dissolve each tablet in 4 mL aqueous solution of 0.2 N HCl. For ingesting the resulting mixture, they should use a drinking straw so as to avoid contact with the teeth. This administration should be followed with a cup of tap water.

Information For Patients

Patients should be instructed to report any signs and symptoms which may suggest liver dysfunction so that appropriate biochemical testing can be done. Such signs and symptoms may include unusual fatigue, anorexia, nausea and/or vomiting, jaundice, dark urine or pale stools (see WARNINGS section).

Drug Interactions

Ketoconazole is a potent inhibitor of the cytochrome P450 3A4 enzyme system. Coadministration of ketoconazole tablets and drugs primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentrations of the drugs that could increase or prolong both therapeutic and adverse effects. Therefore, unless otherwise specified, appropriate dosage adjustments may be necessary. The following drug interactions have been identified involving ketoconazole tablets and other drugs metabolized by the cytochrome P450 enzyme system.Ketoconazole tablets inhibit the metabolism of terfenadine, resulting in an increased plasma concentration of terfenadine and a delay in the elimination of its acid metabolite. The increased plasma concentration of terfenadine or its metabolite may result in prolonged QT intervals. (See BOX WARNING, CONTRAINDICATIONS, and WARNINGS sections.)Pharmacokinetic data indicate that oral ketoconazole inhibits the metabolism of astemizole, resulting in elevated plasma levels of astemizole and its active metabolite desmethylastemizole which may prolong QT intervals. Coadministration of astemizole with ketoconazole tablets is therefore contraindicated. (See BOX WARNING, CONTRAINDICATIONS, and WARNINGS sections.)Human pharmacokinetic data indicate that oral ketoconazole potentially inhibits the metabolism of cisapride resulting in a mean eight-fold increase in AUC of cisapride. Data suggest that coadministration of oral ketoconazole and cisapride can result in prolongation of the QT interval on the ECG. Therefore concomitant administration of ketoconazole tablets with cisapride is contraindicated. (See BOX WARNING, CONTRAINDICATIONS, and WARNINGS sections.)Ketoconazole tablets may alter the metabolism of cyclosporine, tacrolimus, and methylprednisolone, resulting in elevated plasma concentrations of the latter drugs. Dosage adjustment may be required if cyclosporine, tacrolimus, or methylprednisolone are given concomitantly with ketoconazole tablets.Coadministration of ketoconazole tablets with midazolam and triazolam has resulted in elevated plasma concentrations of the latter two drugs. This may potentiate and prolong hypnotic and sedative effects, especially with repeated dosing or chronic administration of these agents. These agents should not be used in patients treated with ketoconazole tablets. If midazolam is administered parenterally, special precaution is required since the sedative effect may be prolonged.Rare cases of elevated plasma concentrations of digoxin have been reported. It is not clear whether this was due to the combination of therapy. It is, therefore, advisable to monitor digoxin concentrations in patients receiving ketoconazole.When taken orally, imidazole compounds like ketoconazole may enhance the anticoagulant effect of coumarin-like drugs. In simultaneous treatment with imidazole drugs and coumarin drugs, the anticoagulant effect should be carefully titrated and monitored.Because severe hypoglycemia has been reported in patients concomitantly receiving oral miconazole (an imidazole) and oral hypoglycemic agents, such a potential interaction involving the latter agents when used concomitantly with ketoconazole tablets (an imidazole) can not be ruled out.Concomitant administration of ketoconazole tablets with phenytoin may alter the metabolism of one or both of the drugs. It is suggested to monitor both ketoconazole and phenytoin.Concomitant administration of rifampin with ketoconazole tablets reduces the blood levels of the latter. INH (isoniazid) is also reported to affect ketoconazole concentrations adversely. These drugs should not be given concomitantly.After the coadministration of 200 mg oral ketoconazole twice daily and one 20 mg dose of loratadine to 11 subjects, the AUC and Cmax of loratadine averaged 302% (± 142 S.D.) and 251% (± 68 S.D.), respectively, of those obtained after co-treatment with placebo. The AUC and Cmax of descarboethoxyloratadine, an active metabolite, averaged 155% (± 27 S.D.) and 141% (± 35 S.D.), respectively. However, no related changes were noted in the QTc on ECG taken at 2, 6, and 24 hours after the coadministration. Also, there were no clinically significant differences in adverse events when loratadine was administered with or without ketoconazole.Rare cases of a disulfiram-like reaction to alcohol have been reported. These experiences have been characterized by flushing, rash, peripheral edema, nausea, and headache. Symptoms resolved within a few hours.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

The dominant lethal mutation test in male and female mice revealed that single oral doses of ketoconazole as high as 80 mg/kg produced no mutation in any stage of germ cell development. The Ames Salmonella microsomal activator assay was also negative. A long term feeding study in Swiss Albino mice and in Wistar rats showed no evidence of oncogenic activity.

Pregnancy Category C

Ketoconazole has been shown to be teratogenic (syndactylia and oligodactylia) in the rat when given in the diet at 80 mg/kg/day (10 times the maximum recommended human dose). However, these effects may be related to maternal toxicity, evidence of which also was seen at this and higher dose levels.There are no adequate and well controlled studies in pregnant women. Ketoconazole should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Ketoconazole has also been found to be embryotoxic in the rat when given in the diet at doses higher than 80 mg/kg during the first trimester of gestation. In addition, dystocia (difficult labor) was noted in rats administered oral ketoconazole during the third trimester of gestation. This occurred when ketoconazole was administered at doses higher than 10 mg/kg (higher than 1.25 times the maximum human dose).It is likely that both the malformations and the embryotoxicity resulting from the administration of oral ketoconazole during gestation are a reflection of the particular sensitivity of the female rat to this drug. For example, the oral LD50 of ketoconazole given by gavage to the female rat is 166 mg/kg whereas in the male rat the oral LD50 is 287 mg/kg.

Nursing Mothers

Since ketoconazole is probably excreted in the milk, mothers who are under treatment should not breast feed.

Pediatric Use

Ketoconazole tablets have not been systematically studied in children of any age, and essentially no information is available on children under 2 years. Ketoconazole should not be used in pediatric patients unless the potential benefit outweighs the risks.

Adverse Reactions

In rare cases, anaphylaxis has been reported after the first dose. Several cases of hypersensitivity reactions including urticaria have also been reported. However, the most frequent adverse reactions were nausea and/or vomiting in approximately 3%, abdominal pain in 1.2%, pruritus in 1.5%, and the following in less than 1% of the patients: headache, dizziness, somnolence, fever and chills, photophobia, diarrhea, gynecomastia, impotence, thrombocytopenia, leukopenia, hemolytic anemia, and bulging fontanelles. Oligospermia has been reported in investigational studies with the drug at dosages above those currently approved. Oligospermia has not been reported at dosages up to 400 mg daily, however sperm counts have been obtained infrequently in patients treated with these dosages. Most of these reactions were mild and transient and rarely required discontinuation of ketoconazole tablets. In contrast, the rare occurrences of hepatic dysfunction require special attention (see WARNINGS section).In worldwide postmarketing experience with ketoconazole tablets there have been rare reports of alopecia, paresthesia, and signs of increased intracranial pressure including bulging fontanelles and papilledema. Hypertriglyceridemia has also been reported but a causal association with ketoconazole is uncertain.Neuropsychiatric disturbances, including suicidal tendencies and severe depression, have occurred rarely in patients using ketoconazole tablets.Ventricular dysrhythmias (prolonged QT intervals) have occurred with the concomitant use of terfenadine with ketoconazole tablets. (See BOX WARNING, CONTRAINDICATIONS, and WARNINGS sections.)Data suggest that coadministration of ketoconazole tablets and cisapride can result in prolongation of the QT interval and has rarely been associated with ventricular arrhythmias. (See CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS sections.)

Overdosage

In the event of accidental overdosage, supportive measures, including gastric lavage with sodium bicarbonate, should be employed.

Adults

The recommended starting dose of ketoconazole tablets is a single daily administration of 200 mg (one tablet). In very serious infections or if clinical responsiveness is insufficient within the expected time, the dose of ketoconazole may be increased to 400 mg (two tablets) once daily.

Children

In small numbers of children over 2 years of age, a single daily dose of 3.3 to 6.6 mg/kg has been used. Ketoconazole tablets have not been studied in children under 2 years of age.There should be laboratory as well as clinical documentation of infection prior to starting ketoconazole therapy. Treatment should be continued until tests indicate that active fungal infection has subsided. Inadequate periods of treatment may yield poor response and lead to early recurrence of clinical symptoms. Minimum treatment for candidiasis is one or two weeks. Patients with chronic mucocutaneous candidiasis usually require maintenance therapy. Minimum treatment for the other indicated systemic mycoses is six months.Minimum treatment for recalcitrant dermatophyte infections is four weeks in cases involving glabrous skin. Palmar and plantar infections may respond more slowly. Apparent cures may subsequently recur after discontinuation of therapy in some cases.

How Supplied

Ketoconazole is available as white to off-white round, flat tablets, scored on one side, engraved T57 on the side of the score, containing 200 mg of ketoconazole. They are supplied in bottles of: 30 tablets (NDC 60429-020-30)90 tablets (NDC 60429-020-90) 100 tablets (NDC 60429-020-01)

Storage

Store at room temperature (59°-86°F/15°-30°C).Protect from moisture.Revised March 1999Mfd. by: Taro Pharmaceutical Industries Ltd. Haifa Bay, Israel 26110Marketed/Packaged by: GSMS Inc. Camarillo, CA 93012

* Please review the disclaimer below.